Table 1 Large-scale randomized controlled trials of SGLT2i
Trial name | Population(n) | CVD (%) | T2DM (%) | eGFR | Intervention | Median follow–up (years) | Primary outcomes HR (95% CI) | HHF HR (95% CI) | DCC HR (95%CI) | DAC HR (95%CI) | FNMI HR (95%CI) | FNS HR (95%CI) | Other outcomes HR/AD (95%CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMPA-REG OUTCOME | 7,020 with T2DM and established CVD |  > 99 | 100 |  ≥ 30 | Empagliflozin 10 mg or 25 mg versus placebo | 3.1 | MACE 0.86 (0.74–0.99) | 0.65 (0.50–0.85) | 0.62 (0.49–0.77) | 0.68 (0.57–0.82) | 0.87 (0.70–1.09) | 1.18 (0.89–1.56) |  |
EMPEROR-Reduced | 3,730 patients with HFrEF and NYHA class II–IV symptoms | 100 | 50 | NA | Empagliflozin 10 mg versus placebo | 1.3 | HHF or DCC 0.75 (0.65–0.86) | 0.69 (0.59–0.81) | 0.92 (0.75–1.12) | 0.92 (0.77–1.10) | NA | NA | Change in KCCQ score 1.7 (0.5–3.0) |
CANVAS Program | 10,142 patients with T2DM and established CVD or multiple cardiovascular risk factors | 66 | 100 |  ≥ 30 | Canagliflozin 100 mg or 300 mg versus placebo | 2.4 | MACE 0.86 (0.75–0.97) | 0.67 (0.52–0.87) | 0.87 (0.72–1.06) | 0.87 (0.74–1.01) | 0.89 (0.73–1.09) | 0.87 (0.69–1.09) |  |
CREDENCE | 4,401 patients with T2DM and albuminuric chronic kidney disease | 50 | 100 | 30–89 | Canagliflozin 100 mg versus placebo | 2.6 | ESKD, a doubling of serum creatinine level, or renal or cardiovascular death 0.70 (0.59–0.82) | 0.61 (0.47–0.80) | 0.78 (0.61–1.00) | 0.83 (0.68–1.02) | NA | NA |  |
DECLARE-TIMI 58 | 17,160 patients with T2DM and established ASCVD or multiple risk factors for ASCVD | 41 | 100 |  ≥ 60 | Dapagliflozin 10 mg versus placebo | 4.2 | HHF or DCC 0.83 (0.73–0.95); MACE 0.93 (0.84–1.03) | 0.73 (0.61–0.88) | 0.98 (0.82–1.17) | 0.93 (0.82–1.04) | 0.89 (0.77–1.01) | 1.01 (0.84–1.21) |  |
DAPA-HF | 4,744 patients with HFrEF and NYHA class II–IV symptoms | 100 | 45 |  ≥ 30 | Dapagliflozin 10 mg versus placebo | 1.5 | Hospitalization or urgent visit with intravenous therapy for HF or DCC 0.74 (0.65–0.85) | 0.70 (0.59–0.83) | 0.82 (0.69–0.98) | 0.83 (0.71–0.97) | NA | NA | Change in KCCQ score 1.18 (1.11–1.26); DCC or HHF 0.75 (0.65–0.85) |
DAPA-CKD | 4,304 patients with an eGFR of 25–75 ml/min/1.73m2 and a urinary albumin-to-creatinine ratio of 200–5000 | 37 | 68 | 25–75 | Dapagliflozin 10 mg versus placebo | 2.4 | ESKD, sustained decline in the eGFR of 50%, or renal or cardiovascular death 0.61 (0.51–0.72) | NA | 0.81 (0.58–1.12) | 0.69 (0.53–0.88) | NA | NA | DCC or HHF 0.71 (0.55–0.92) |
VERTIS-CV | 8,246 patients with T2DM and ASCVD | 100 | 100 |  ≥ 30 | Ertugliflozin 5 mg or 15 mg versus placebo | 3.0 | MACE 0.97 (0.85–1.11) | 0.70 (0.54–0.90) | 0.92 (0.77–1.11) | 0.93 (0.80–1.08) | 1.04 (0.86–1.26) | 1.06 (0.82–1.37) | DCC or HHF 0.88 (0.75–1.03) |
SOLOIST-WHF | 1,222 patients with T2DM and hospitalization for worsening heart failure | 100 | 100 |  ≥ 30 | Sotagliflozin 200 mg or 400 mg versus placebo | 0.75 | Hospitalization or urgent visit for HF or DCC 0.67 (0.52–0.85) | 0.64 (0.49–0.83) | 0.84 (0.58–1.22) | 0.82 (0.59–1.14) | NA | NA | Change in KCCQ score 4.1 (1.3–7.0); Primary outcomes in patients with HFpEF 0.48 (0.27–0.86) |